Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01967771
Other study ID # 200901
Secondary ID
Status Completed
Phase Phase 1
First received October 4, 2013
Last updated January 23, 2014
Start date October 2013
Est. completion date January 2014

Study information

Verified date January 2014
Source ViiV Healthcare
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

This study will be a phase I, open label, three period, fixed sequence crossover study to evaluate the effect of Carbamazepine (CBZ) on the steady-state pharmacokinetics of Dolutegravir (DTG) and on the safety and tolerability of DTG. Subjects will have a screening visit within 30 days prior to the first dose of study drug, three treatment periods, and a follow-up visit 7-14 days after the last dose of study drug. There is no washout between treatment periods.


Recruitment information / eligibility

Status Completed
Enrollment 16
Est. completion date January 2014
Est. primary completion date January 2014
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria:

- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including [medical history, physical examination, laboratory tests and cardiac monitoring]. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.

- Male/females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.

- A female subject is eligible to participate if she is of: non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, bilateral oophorectomy or hysterectomy [for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >40 milli international units per milliliter (MIU/mL) and estradiol <40 picograms (pg)/mL (<147 picomole per liter (pmol/L) is confirmatory]; Child-bearing potential with negative pregnancy test as determined by [serum or urine] human chorionic gonadotropin (hCG) test at screening or prior to dosing AND Agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 5 days post-last dose. OR has only same-sex partners, when this is her preferred and usual lifestyle.

- Body weight >=50 kilograms (Kg) for males and >=45 Kg for females and body mass index (BMI) within the range 18.5 - 31.0 Kg/m^2 (square meters) (inclusive).

- Alanine aminotransferase, alkaline phosphatase and bilirubin <= 1.5x Upper Limit of Normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat is allowed for eligibility determination.

- Based on single corrected QT interval (QTc) value: QT duration corrected for heart rate by Bazett's formula (QTcB) <450 millisecond (msec); or QTc <480 msec in subjects with Bundle Branch Block.

- A negative HLA-B*1502 allele screening assessment for subjects of Asian ethnicity only.

- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

Exclusion Criteria:

- A positive pre-study drug/alcohol screen.

- A positive test for human immunodeficiency virus (HIV) antibody.

- Pregnant females as determined by positive [serum or urine] hCG test at screening or prior to dosing.

- History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.

- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation. Subjects will allergy to tricyclic antidepressants should not be enrolled.

- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

- Lactating females.

- The subject's systolic blood pressure is outside the range of 90-140 millimeters of mercury (mmHg), or diastolic pressure is outside the range of 45-90 mmHg, or heart rate is outside the range of 50-100 beats per minute (bpm) for female subjects or 45-100 bpm for male subjects. A single repeat is allowed for eligibility determination.

- Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Heart rate for males <45 and >110 bpm and females <50 and >100 bpm; PR interval <120 and >220 msec, QRS duration <70 and >120 msec, QTc interval (Bazett) >450 msec. Evidence of previous myocardial infarction (Does not include ST segment changes associated with repolarization); any clinically significant arrhythmia which, in the opinion of the investigator and GSK Medical Monitor, will interfere with the safety for the individual subject; any conduction abnormality (including but not specific to left or right incomplete bundle branch block, atrioventricular block [2nd degree or higher], Wolf Parkinson White [WPW] syndrome), sinus pauses>3 seconds, and non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats).

- Platelets, white blood cell count or hemoglobin below the lower limit of normal. A single repeat is allowed for eligibility determination.

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

- History of suicide ideation or severe depression.

- History of hepatic porphyria (e.g., acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda.

- History of previous bone marrow depression (e.g., prior viral or drug related bone marrow depression)

- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St. John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.

- Unwillingness or inability to follow the procedures outlines in the protocol.

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label


Related Conditions & MeSH terms


Intervention

Drug:
DTG
DTG will be supplied as 50 mg tablet to be administered orally
CBZ
CBZ will be supplied as 100 mg and 200 mg extended release tablet to be administered orally

Locations

Country Name City State
United States GSK Investigational Site Overland Park Kansas

Sponsors (2)

Lead Sponsor Collaborator
ViiV Healthcare GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Steady state plasma DTG pharmacokinetics (PK) parameters PK parameters will include: Steady state plasma DTG concentration at the end of the dosing interval (Ctau), maximum concentration (Cmax), area under the time-concentration curve over the dosing interval [AUC(0-tau)], apparent clearance following oral dosing (CL/F), terminal phase half life (t1/2), concentration at time zero (C0) and minimum concentration (Cmin) Day 5 and Day 26 No
Secondary Change from baseline in 12-lead electrocardiogram (ECG) Single 12-lead ECGs will be obtained at each timepoint Up to 40 days No
Secondary Change from baseline in vital signs Vital signs will include systolic and diastolic blood pressure and pulse rate Up to 40 days No
Secondary Number of subjects with adverse events (AEs) AEs will be assessed throughout the study Up to 40 days No
Secondary Toxicity grading of clinical laboratory tests Laboratory assessments will include haematology, clinical chemistry and urinalysis parameters Up to 40 days No
See also
  Status Clinical Trial Phase
Completed NCT01425099 - Drug Interaction Study Between Dolutegravir and Prednisone Phase 1
Completed NCT01209117 - A Study to Assess the Relative Bioavailability of Tablet Formulations of GSK2248761 in Healthy Adult Subjects. SGN114435 Phase 1
Completed NCT03231943 - GSK3640254 First Time in Human (FTIH) Study in Healthy Volunteers Phase 1
Terminated NCT01195974 - A Study to Evaluate the Pharmacokinetics of an Oral Contraceptive When Co-administered With GSK2248761 in Healthy Adult Female Subjects. Phase 1
Completed NCT02893488 - Relative Bioavailability Study of a Fixed-dose Combination Dolutegravir/Abacavir/Lamivudine Dispersible Tablet Phase 1
Terminated NCT01199731 - Dose-finding Study of GSK2248761 in Antiretroviral Therapy-experienced Subjects With NNRTI-resistant HIV Infection Phase 2
Completed NCT01449929 - Dolutegravir Compared to Darunavir/Ritonavir , Each in Combination With Dual Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in ART-naive Subjects Phase 3
Active, not recruiting NCT02951052 - Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine From Current Antiretroviral Regimen in Virologically Suppressed HIV-1-infected Adults Phase 3
Completed NCT01231516 - A Study of GSK1349572 Versus Raltegravir (RAL) With Investigator Selected Background Regimen in Antiretroviral-Experienced, Integrase Inhibitor-Naive Adults Phase 3
Completed NCT02273947 - Food Effect Study With BMS-955176 Phase 1
Completed NCT00071760 - Study Of An Investigational Regimen Including FDA Approved HIV Drugs In HIV-Infected Pediatric Subjects Phase 2
Completed NCT02539576 - Pharmacokinetics, Safety and Tolerability Study of Abacavir/ Dolutegravir/ Lamivudine Fixed-dose Combination Tablets in Healthy Japanese Subjects Phase 1
Completed NCT00774735 - GSK1349572 Drug Interaction Study With Protease Inhibitors Phase 1
Completed NCT01077635 - PENTA Fosamprenavir Study N/A
Completed NCT00386347 - A Study To Evaluate Formulations And Food Effect On GSK364735 In Healthy Subjects. Phase 1
Completed NCT00945282 - Safety and Tolerability Study to Evaluate Lower Dose of GSK2248761 in Antiretroviral Treatment-Naive HIV-1 Infected Adults. Phase 2
Terminated NCT02576119 - A Study to Determine the Effect of Multiple Doses of BMS-955176 on the Electrocardiograph of Healthy Subjects Phase 1
Completed NCT02277600 - A Phase 1 Antiretroviral Drug-Drug Interaction Study in Healthy Volunteers (DDI) Phase 1
Completed NCT00398125 - Monotherapy Versus Placebo Over 10 Days in Integrase Naive HIV-1 Infected Adults Phase 2
Completed NCT01077557 - Fractures Stratified by HIV and Antiretroviral Therapy (ART) Status N/A